Skp2 Inhibitor C1(SKPin C1) is a specific small molecule inhibitor of Skp2-mediated p27 degradation, selectively inhibited Skp2-mediated p27 degradation by reducing p27 binding through key compound-receptor contacts.IC50 value: Target: Skp2 inhibitor; p27 regulatorin vitro: T47D cells treated with C1 (5 μM for 16 hours) displayedan increase in G1 phase (p < 0.0001) and a decrease in S phase (p < 0.0001), correlating with p27 protein induction. In contrast, MCF-7 cells responded to C1 with a significant reduction in G1 phase (35%, p < 0.0001) and an increase in G2-M phase (43%, p < 0.0001). This G1 reduction and G2/M arrest is dose dependent on C1 (Figure 5C right; p < 0.001 and p < 0.01, respectively) and correlates with increased p27 protein levels (Figure 5E left, S4A top right) [1].
[1]. Wu L, et al. Specific small molecule inhibitors of Skp2-mediated p27 degradation. Chem Biol. 2012 Dec 21;19(12):1515-24. [2]. Pavlides SC, et al. Inhibitors of SCF-Skp2/Cks1 E3 ligase block estrogen-induced growth stimulation and degradation of nuclear p27kip1: therapeutic potential for endometrial cancer. Endocrinology. 2013 Nov;154(11):4030-45.